Retracted: Post‐transcriptional regulation of the let‐7 microRNA during neural cell specification

Abstract

The let-7 miRNA regulates developmental timing in C. elegans and is an important paradigm for investigations of miRNA functions in mammalian development. We have examined the role of miRNA precursor processing in the temporal control and lineage specificity of the let-7 miRNA. In situ hybridization (ISH) in E9.5 mouse embryos revealed early induction of let-7 in the developing central nervous system. The expression pattern of three let-7 family members closely resembled that of the brain-enriched miRNAs mir-124, mir-125 and mir-128. Comparison of primary, precursor, and mature let-7 RNA levels during both embryonic brain development and neural differentiation of embryonic stem cells and embryocarcinoma (EC) cells suggest post-transcriptional regulation of let-7 accumulation. Reflecting these results, let-7 sensor constructs were strongly down-regulated during neural differentiation of EC cells and displayed lineage specificity in primary cells. Neural differentiation of EC cells was accompanied by an increase in let-7 precursor processing activity in vitro. Furthermore, undifferentiated and differentiated cells contained distinct precursor RNA binding complexes. A neuron-enhanced binding complex was shown by antibody challenge to contain the miRNA pathway proteins Argonaute1 and FMRP. Developmental regulation of the processing pathway correlates with differential localization of the proteins Argonaute, FMRP, MOV10, and TNRC6B in self-renewing stem cells and neurons.

New meaning in the message: Noncoding RNAs and their role in retinal development

“…By contrast, the pri-form of the highly retinal-enriched miR-96/182/ 183 cluster is barely detectable even by RT-PCR, so abundance of some primiRNAs is unlikely to reflect general deficiencies in miRNA processing in retina . It is not yet clear what role, if any, these abundant primiRNAs may be playing in the retina, although high levels of other unprocessed pri-miRNAs have also recently been observed in embryonic tissue and cancer cells (Thomson et al, 2006), and this has led to the proposal that primiRNA processing by Drosha may be regulated in certain circumstances (Wulczyn et al, 2007). The recent discovery that activated Smads can associate with the Drosha complex and regulate its activity suggests a possible mechanism by which this could occur.…”

Bone morphogenetic protein-2 down-regulates miR-206 expression by blocking its maturation process

“…Post-transcriptional regulation of miRNA expression has been reported to occur in a tissue-specific [16] and developmentally-regulated fashion [17]. In addition, certain pri-miRNAs are highly expressed in human and mouse embryonic stem cells, and tumors; however, the corresponding mature miRNAs are not detectable, which suggests that there may be a block in miRNA biogenesis [18].…”

Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2

“…Pre-miRNAs are then exported to the cytoplasm, where they are processed into mature miRNAs by the Dicer/TRBP complex (Kim 2005). Post-transcriptional control of miRNA maturation occurs in a tissue-specific and developmentally regulated manner (Mineno et al 2006;Obernosterer et al 2006; Thomson et al 2006;Wulczyn et al 2007). Several pri-miRNAs accumulate to high levels in human and mouse embryonic stem (ES) cells, mouse embryocarcinoma (EC) cells, and human primary tumors, where their cropping is blocked (Suh et al 2004; Thomson et al 2006).…”